The herpesviruses are the largest and most complex viruses known to have definite etiological connections with cancer in animals and man. There are five distinct human herpesviruses, herpes simplex types 1 and 2, cytomegalovirus, Epstein-Barr virus and varicella-zoster virus: all are harbored as latent infections in vitrually the entire adult population and can cause clinical disease especially in the young and immunologically deficient. The DNA genomes of human herpesviruses are of particular interest for two reasons. Firstly, because in most cases, a small but as yet unidentified portion of the DNA is capable of inducing stable malignant cell transformation and secondly, because they are structurally interesting and readily accessible pieces of DNA that encode and express regulated and meaningful functions within a eukaryotic cellular environment. Preliminary work with herpes simplex virus DNA has shown that it is readily accessible to study the dissection by modern electron microscopic, restriction enzyme and gel electrophoresis technologies and that such studies are likely to yield a great deal of information about the functional and evolutionary significance of inverted duplications and tandemly reiterated sequences as well as about the mechanisms of DNA replication and recombination. In addition, we hope to be able to identify and study in detail that portion of the herpes virus genome responsible for initiating and maintaining transformation. Some understanding of the role of the "transforming" genes in the life cycle of the virus would provide an important and necessary first step in evaluating the possibilities for eventual control of infections with these viruses and possibly of oncogenic transformation events as well.